Identification of early diagnosis markers of pancreatic ductal adenocarcinoma (PDAC) using publicly available transcriptomic tumor and blood sample data

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most frequently diagnosed form of pancreatic cancer worldwide. PDAC is associated with poor survival rate mainly due to the disease being usually diagnosed at late stages. Publicly available gene expression data from 10 studies with tumour tissue (448 samples) and/or blood samples (128 samples) from PDAC patients were pooled together and analysed for the identification of stage-specific (American Joint Committee for Cancer, AJCC staging) and global diagnostic markers. Validation of markers was performed using Cancer Genome Atlas (TCGA) PDAC expression data. Differential gene expression analysis was carried out to compare tumour and normal samples (stage-specific tissue samples vs. normal tissue samples and stage-agnostic blood samples vs. normal blood samples). Active subnetwork search and miRNA enrichment analysis were used to identify enriched gene networks and miRNA interactions. We identified 820 consistently deregulated genes in tissue samples of all stages and blood samples. Active subnetwork analysis revealed enriched ribosome, proteasome, adherens junction and cell cycle pathways across all stages and blood samples suggesting biological plausibility. Stage-specific enriched miRNAs with diagnostic potential were also identified (miR-21, miR-29, miR-124, miR-30, for stages 1-4 respectively). Extensive gene expression deregulation was found in all tumor stages with significant overlap. Additionally, miRNA contribution to PDAC pathology may be important and probably mediated by distinct miRNAs in each stage of PDAC. We therefore present a list of markers and miRNAs that could potentially act as a diagnostic tool for early detection of PDAC onset.